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Evidence-based patient blood management guidelines commonly recommend restrictive hemoglobin thresholds of 70 to 80 g/L for asymptomatic adults. However, most transfusion trials have enrolled adults across a broad age span, with few exclusive to older adults. Our recent meta-analysis of transfusion trials that focused on older adults paradoxically found lower mortality and fewer cardiac complications when these patients were managed using higher hemoglobin thresholds. We postulate that declining cardiac output with age contributes to deteriorating oxygen delivery capacity which impacts anemia-associated outcomes in older adults and propose a model to explain this age-related difference. We reviewed evidence concerning the pathophysiology of aging to explore the disparity in transfusion trial outcomes related to hemoglobin thresholds in different age groups. The literature was searched for normative cardiac output values at different ages in healthy adults. Using normative peak cardiac output data, we modeled oxygen delivery capacity in young, middle-aged, and older adults at a range of hemoglobin levels. Cardiovascular and pulmonary systems are impacted by age-related pathophysiological changes. Diminishing peak cardiac output associated with aging reduces the maximal oxygen delivery achievable under metabolic stress. Hence, at low hemoglobin levels, older adults are more susceptible to tissue hypoxia than younger adults. Our model predicts that an older adult with a hemoglobin of 100 g/L has a similar peak oxygen delivery capacity to a young adult with a hemoglobin of 70 g/L. Age-related pathophysiological changes provide some explanation as to why older adults have a lower tolerance for anemia than younger adults. This indicates the need for patient blood management hemoglobin thresholds specific to older as distinct from younger adults. The primary application of this model is in the consideration of patients rehabilitating to life outside hospital. It is important to note that pathophysiological changes associated with critical illness and major surgery are more complex than can be described in a simple model based on cardiac output and hemoglobin concentration. However, our review of oxygen transport and delivery in health and disease states allows the model to be considered in the context of treatment decisions for anemic adults in a range of hospital and community settings., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Guidelines for patient blood management recommend restrictive transfusion practice for most adult patients. These guidelines are supported by evidence from randomised controlled trials (RCTs); however, one of the patient groups not explicitly examined in these studies is the geriatric population. We examined RCTs relevant to transfusion outcomes in older patients. Our aim was to determine whether special guidelines are warranted for geriatric patients, recognising the different pathophysiological characteristics of this group., Methods: For this systematic review and meta-analysis, we searched PubMed, Scopus, and the Cochrane Library databases from their inception to May 5, 2017, for evidence relating to transfusion outcomes in adults aged 65 years and older. This criterion was widened to include RCTs where a substantial proportion of the study population was older than 65 years. We also included study populations of all clinical settings, and did not limit the search by date, language, or study type. For articles not in English, only available translations of the abstracts were reviewed. Studies were excluded if they did not specify age. Observational studies and duplicate patient and outcome data from studies that generated multiple publications were also excluded. We screened bibliographies of retrieved articles for additional publications. We analysed data extracted from published RCTs comparing restrictive and liberal transfusion strategies in older adults. We generated fixed effects risk ratios (RR) for pooled study data using the Mantel-Haenszel method. Primary outcomes were 30-day and 90-day mortality events for patients enrolled in restrictive and liberal transfusion study groups. We included intention-to-treat outcome data in the meta-analysis when available, otherwise we used per-protocol outcome data., Findings: 686 articles were identified by the search, and a further 37 by the snowball approach. Of these articles, 13 eligible papers described findings from nine RCTs (five trials investigating orthopaedic surgery, three cardiac surgery, and one oncology surgery; including 5780 patients). The risk of 30-day mortality was higher in older patients who followed a restrictive transfusion strategy than in those who followed a liberal transfusion strategy (risk ratio [RR] 1·36, 95% CI 1·05-1·74; p=0·017). The risk of 90-day mortality was also higher in those who followed a restrictive transfusion strategy than in those who followed a liberal transfusion strategy (RR 1·45, 95% CI 1·05-1·98; p=0·022)., Interpretation: Liberal transfusion strategies might produce better outcomes in geriatric patients than restrictive transfusion strategies. This outcome contradicts current restrictive transfusion approaches. Population ageing will challenge resources globally, and this finding has implications for blood supply and demand, and optimal care of older adults. Further research is needed to formulate evidence-based transfusion practice across clinical specialties specific to the geriatric population, and to examine resource effects., Funding: Australia's National Blood Authority., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The purpose of this study was to determine the effects of smoke induced acute lung injury (S-ALI), extracorporeal membrane oxygenation (ECMO) and transfusion on oxidative stress and plasma selenium levels. Forty ewes were divided into (i) healthy control (n=4), (ii) S-ALI control (n=7), (iii) ECMO control (n=7), (iv) S-ALI+ECMO (n=8) and (v) S-ALI+ECMO+packed red blood cell (PRBC) transfusion (n=14). Plasma thiobarbituric acid reactive substances (TBARS), selenium and glutathione peroxidase (GPx) activity were analysed at baseline, after smoke injury (or sham) and 0.25, 1, 2, 6, 7, 12 and 24h after initiation of ECMO. Peak TBARS levels were similar across all groups. Plasma selenium decreased by 54% in S-ALI sheep (1.36±0.20 to 0.63±0.27μmol/L, p<0.0001), and 72% in sheep with S-ALI+ECMO at 24h (1.36±0.20 to 0.38±0.19, p<0.0001). PRBC transfusion had no effect on TBARS, selenium levels or glutathione peroxidase activity in plasma. While ECMO independently increased TBARS in healthy sheep to levels which were similar to the S-ALI control, the addition of ECMO after S-ALI caused a negligible increase in TBARS. This suggests that the initial lung injury was the predominant feature in the TBARS response. In contrast, the addition of ECMO in S-ALI sheep exacerbated reductions in plasma selenium beyond that of S-ALI or ECMO alone. Clinical studies are needed to confirm the extent and duration of selenium loss associated with ECMO., (Crown Copyright © 2015. Published by Elsevier GmbH. All rights reserved.)

Background: The growing awareness of transfusion-associated morbidity and mortality necessitates investigations into the underlying mechanisms. Small animals have been the dominant transfusion model but have associated limitations. This study aimed to develop a comprehensive large animal (ovine) model of transfusion encompassing: blood collection, processing and storage, compatibility testing right through to post-transfusion outcomes., Materials and Methods: Two units of blood were collected from each of 12 adult male Merino sheep and processed into 24 ovine-packed red blood cell (PRBC) units. Baseline haematological parameters of ovine blood and PRBC cells were analysed. Biochemical changes in ovine PRBCs were characterized during the 42-day storage period. Immunological compatibility of the blood was confirmed with sera from potential recipient sheep, using a saline and albumin agglutination cross-match. Following confirmation of compatibility, each recipient sheep (n = 12) was transfused with two units of ovine PRBC., Results: Procedures for collecting, processing, cross-matching and transfusing ovine blood were established. Although ovine red blood cells are smaller and higher in number, their mean cell haemoglobin concentration is similar to human red blood cells. Ovine PRBC showed improved storage properties in saline-adenine-glucose-mannitol (SAG-M) compared with previous human PRBC studies. Seventy-six compatibility tests were performed and 17·1% were incompatible. Only cross-match compatible ovine PRBC were transfused and no adverse reactions were observed., Conclusion: These findings demonstrate the utility of the ovine model for future blood transfusion studies and highlight the importance of compatibility testing in animal models involving homologous transfusions., (© 2013 International Society of Blood Transfusion.)

Transfusion-related acute lung injury (TRALI) is the most common cause of serious morbidity and mortality due to hemotherapy. Although the pathogenesis has been related to the infusion of donor antibodies into the recipient, antibody negative TRALI has been reported. Changes in transfusion practices, especially the use of male-only plasma, have decreased the number of antibody-mediated cases and deaths; however, TRALI still occurs. The neutrophil appears to be the effector cell in TRALI and the pathophysiology is centered on neutrophil-mediated endothelial cell cytotoxicity resulting in capillary leak and ALI. This review will detail the pathophysiology of TRALI including recent pre-clinical data, provide insight into newer areas of research, and critically assess current practices to decrease it prevalence and to make transfusion safer.

Transfusion practice, like medical practice in its entirety, has evolved rapidly over the past few decades. Recent research on clinical outcomes has examined the impact of blood transfusion on critically ill patients, patients with trauma, those undergoing cardiac surgery, those experiencing acute coronary syndromes, oncology patients and others. Evidence is mounting of adverse outcomes associated with blood transfusion in a wide variety of clinical contexts. Here, we highlight the deficit in the current literature guiding transfusion practice, and call for an Australasian study to fill this deficit.